The molecular mechanism of the antagonistic activity of hydroxylated polybrominated biphenyl (OH-BB80) toward thyroid receptor beta

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境水质学国家重点实验室

	The molecular mechanism of the antagonistic activity of hydroxylated polybrominated biphenyl (OH-BB80) toward thyroid receptor beta
	Zhang, Xiaofang ; Cui, Shixuan ; Pan, Liumeng ; Dong, Wenhua ; Ma, Mei ; Liu, Weiping ; Zhuang, Shulin
刊名	SCIENCE OF THE TOTAL ENVIRONMENT
	2019-12-20
卷号	697 页码:-
关键词	Hydroxylated brominated biphenyls Endocrine disrupting effect Molecular interactions Metabolic activation
ISSN号	0048-9697
英文摘要	Polybrominated biphenyls (PBBs) were widely used as additive brominated flame retardants. Their hydroxylated products (OH-PBBs) have been detected frequently in various marine mammals, causing an increased health risk. Till now, there lacks information on the potential disruption of OH-PBBs toward thyroid hormone receptor (TR) and the molecular characteristics of their interactions remain largely unknown. We herein in vitro and in silico evaluated the disrupting effect of 3,3',5,5'-tetrabromobiphenyl (BB80) and its metabolite 2,2'-dihydroxy-3,3',5,5'-tetrabromobiphenyl (OH-BB80) toward human TR. The recombinant human TR beta two-hybrid yeast assay reveals the moderate antagonistic activity of OH-BB80 with IC20 at 2 mu mol/L, while BB80 shows no agonistic or antagonistic activity. OH-BB80 binds at the binding cavity of TR beta ligand binding domain (LBD) and forms one hydrogen bond with Phe272. Electrostatic interactions and hydrophobic interactions contribute much to their interactions. The binding of OH-BB80 quenches the intrinsic fluorescence of TR beta LBD at static quenching mode. Our study extends knowledge on the endocrine disrupting effect of OH-PBBs and suggests the full consideration of the biotransformation for further health risk assessment of PBBs and related structurally similar emerging contaminants. (C) 2019 Elsevier B.V. All rights reserved.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/42677]
专题	生态环境研究中心_环境水质学国家重点实验室
作者单位	1.Zhejiang Univ, Coll Environm & Resource Sci, Hangzhou 310058, Zhejiang, Peoples R China 2.Hubei Prov Environm Monitoring Ctr, Wuhan 430072, Hubei, Peoples R China 3.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Key Lab Drinking Water Sci & Technol, Beijing 100085, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiaofang,Cui, Shixuan,Pan, Liumeng,et al. The molecular mechanism of the antagonistic activity of hydroxylated polybrominated biphenyl (OH-BB80) toward thyroid receptor beta[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2019,697:-.
APA	Zhang, Xiaofang.,Cui, Shixuan.,Pan, Liumeng.,Dong, Wenhua.,Ma, Mei.,...&Zhuang, Shulin.(2019).The molecular mechanism of the antagonistic activity of hydroxylated polybrominated biphenyl (OH-BB80) toward thyroid receptor beta.SCIENCE OF THE TOTAL ENVIRONMENT,697,-.
MLA	Zhang, Xiaofang,et al."The molecular mechanism of the antagonistic activity of hydroxylated polybrominated biphenyl (OH-BB80) toward thyroid receptor beta".SCIENCE OF THE TOTAL ENVIRONMENT 697(2019):-.